학술논문
Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas
Document Type
Academic Journal
Author
Abeshouse, Adam; Adebamowo, Clement; Adebamowo, Sally N.; Akbani, Rehan; Akeredolu, Teniola; Ally, Adrian; Anderson, Matthew L.; Anur, Pavana; Appelbaum, Elizabeth L.; Armenia, Joshua; Auman, J. Todd; Bailey, Matthew H.; Baker, Laurence; Balasundaram, Miruna; Balu, Saianand; Barthel, Floris P.; Bartlett, John; Baylin, Stephen B.; Behera, Madhusmita; Belyaev, Dmitry; Bennett, Joesph; Benz, Christopher; Beroukhim, Rameen; Birrer, Michael; Bocklage, Therese; Bodenheimer, Tom; Boice, Lori; Bootwalla, Moiz S.; Bowen, Jay; Bowlby, Reanne; Boyd, Jeff; Brohl, Andrew S.; Brooks, Denise; Byers, Lauren; Carlsen, Rebecca; Castro, Patricia; Chen, Hsiao-Wei; Cherniack, Andrew D.; Chibon, Frederic; Chin, Lynda; Cho, Juok; Chuah, Eric; Chudamani, Sudha; Cibulskis, Carrie; Cooper, Lee A.D.; Cope, Leslie; Cordes, Matthew G.; Crain, Daniel; Curley, Erin; Danilova, Ludmila; Dao, Fanny; Davis, Ian J.; Davis, Lara E.; Defreitas, Timothy; Delman, Keith; Demchok, John A.; Demetri, George D.; Demicco, Elizabeth G.; Dhalla, Noreen; Diao, Lixia; Ding, Li; DiSaia, Phil; Dottino, Peter; Doyle, Leona A.; Drill, Esther; Dubina, Michael; Eschbacher, Jennifer; Fedosenko, Konstantin; Felau, Ina; Ferguson, Martin L.; Frazer, Scott; Fronick, Catrina C.; Fulidou, Victoria; Fulton, Lucinda A.; Fulton, Robert S.; Gabriel, Stacey B.; Gao, Jianjiong; Gao, Qingsong; Gardner, Johanna; Gastier-Foster, Julie M.; Gay, Carl M.; Gehlenborg, Nils; Gerken, Mark; Getz, Gad; Godwin, Andrew K.; Godwin, Eryn M.; Gordienko, Elena; Grilley-Olson, Juneko E.; Gutman, David A.; Gutmann, David H.; Hayes, D. Neil; Hegde, Apurva M.; Heiman, David I.; Heins, Zachary; Helsel, Carmen; Hepperla, Austin J.; Higgins, Kelly; Hoadley, Katherine A.; Hobensack, Shital; Holt, Robert A.; Hoon, Dave B.; Hornick, Jason L.; Hoyle, Alan P.; Hu, Xin; Huang, Mei; Hutter, Carolyn M.; Iacocca, Mary; Ingram, Davis R.; Ittmann, Michael; Iype, Lisa; Jefferys, Stuart R.; Jones, Kevin B.; Jones, Corbin D.; Jones, Steven J.M.; Kalir, Tamara; Karlan, Beth Y.; Karseladze, Apollon; Kasaian, Katayoon; Kim, Jaegil; Kundra, Ritika; Kuo, Hanluen; Ladanyi, Marc; Lai, Phillip H.; Laird, Peter W.; Larsson, Erik; Lawrence, Michael S.; Lazar, Alexander J.; Lee, Sanghoon; Lee, Darlene; Lehmann, Kjong-Van; Leraas, Kristen M.; Lester, Jenny; Levine, Douglas A.; Li, Irene; Lichtenberg, Tara M.; Lin, Pei; Liu, Jia; Liu, Wenbin; Liu, Eric Minwei; Lolla, Laxmi; Lu, Yiling; Ma, Yussanne; Madan, Rashna; Maglinte, Dennis T.; Magliocco, Anthony; Maki, Robert G.; Mallery, David; Manikhas, Georgy; Mardis, Elaine R.; Mariamidze, Armaz; Marra, Marco A.; Martignetti, John A.; Martinez, Cathleen; Mayo, Michael; McLellan, Michael D.; Meier, Sam; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Miller, Christopher A.; Mills, Gordon B.; Moore, Richard A.; Morris, Scott; Mose, Lisle E.; Mozgovoy, Evgeny; Mungall, Andrew J.; Mungall, Karen; Nalisnik, Michael; Naresh, Rashi; Newton, Yulia; Noble, Michael S.; Novak, Janet E.; Ochoa, Angelica; Olvera, Narciso; Owonikoko, Taofeek K.; Paklina, Oxana; Parfitt, Jeremy; Parker, Joel S.; Pastore, Alessandro; Paulauskis, Joseph; Penny, Robert; Pereira, Elena; Perou, Charles M.; Perou, Amy H.; Pihl, Todd; Pollock, Raphael E.; Potapova, Olga; Radenbaugh, Amie J.; Ramalingam, Suresh S.; Ramirez, Nilsa C.; Rathmell, W. Kimryn; Raut, Chandrajit P.; Riedel, Richard F.; Reilly, Colleen; Reynolds, Sheila M.; Roach, Jeffrey; Robertson, A. Gordon; Roszik, Jason; Rubin, Brian P.; Sadeghi, Sara; Saksena, Gordon; Salner, Andrew; Sanchez-Vega, Francisco; Sander, Chris; Schein, Jacqueline E.; Schmidt, Heather K.; Schultz, Nikolaus; Schumacher, Steven E.; Sekhon, Harman; Senbabaoglu, Yasin; Setdikova, Galiya; Shelton, Candace; Shelton, Troy; Shen, Ronglai; Shi, Yan; Shih, Juliann; Shmulevich, Ilya; Sica, Gabriel L.; Simons, Janae V.; Singer, Samuel; Sipahimalani, Payal; Skelly, Tara; Socci, Nicholas; Sofia, Heidi J.; Soloway, Matthew G.; Spellman, Paul; Sun, Qiang; Swanson, Patricia; Tam, Angela; Tan, Donghui; Tarnuzzer, Roy; Thiessen, Nina; Thompson, Eric; Thorne, Leigh B.; Tong, Pan; Torres, Keila E.; van de Rijn, Matt; Van Den Berg, David J.; Van Tine, Brian A.; Veluvolu, Umadevi; Verhaak, Roel; Voet, Doug; Voronina, Olga; Wan, Yunhu; Wang, Zhining; Wang, Jing; Weinstein, John N.; Weisenberger, Daniel J.; Wilkerson, Matthew D.; Wilson, Richard K.; Wise, Lisa; Wong, Tina; Wong, Winghing; Wrangle, John; Wu, Ye; Wyczalkowski, Matthew; Yang, Liming; Yau, Christina; Yellapantula, Venkata; Zenklusen, Jean C.; Zhang, Jiashan, Julia; Zhang, Hailei; Zhang, Hongxin; Zmuda, Erik
Source
Cell. Nov 2, 2017, Vol. 171 Issue 4, 950
Subject
Language
English
ISSN
0092-8674
Abstract
To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/j.cell.2017.10.014 Byline: Adam Abeshouse, Clement Adebamowo, Sally N. Adebamowo, Rehan Akbani, Teniola Akeredolu, Adrian Ally, Matthew L. Anderson, Pavana Anur, Elizabeth L. Appelbaum, Joshua Armenia, J. Todd Auman, Matthew H. Bailey, Laurence Baker, Miruna Balasundaram, Saianand Balu, Floris P. Barthel, John Bartlett, Stephen B. Baylin, Madhusmita Behera, Dmitry Belyaev, Joesph Bennett, Christopher Benz, Rameen Beroukhim, Michael Birrer, Therese Bocklage, Tom Bodenheimer, Lori Boice, Moiz S. Bootwalla, Jay Bowen, Reanne Bowlby, Jeff Boyd, Andrew S. Brohl, Denise Brooks, Lauren Byers, Rebecca Carlsen, Patricia Castro, Hsiao-Wei Chen, Andrew D. Cherniack, Frederic Chibon, Lynda Chin, Juok Cho, Eric Chuah, Sudha Chudamani, Carrie Cibulskis, Lee A.D. Cooper, Leslie Cope, Matthew G. Cordes, Daniel Crain, Erin Curley, Ludmila Danilova, Fanny Dao, Ian J. Davis, Lara E. Davis, Timothy Defreitas, Keith Delman, John A. Demchok, George D. Demetri, Elizabeth G. Demicco, Noreen Dhalla, Lixia Diao, Li Ding, Phil DiSaia, Peter Dottino, Leona A. Doyle, Esther Drill, Michael Dubina, Jennifer Eschbacher, Konstantin Fedosenko, Ina Felau, Martin L. Ferguson, Scott Frazer, Catrina C. Fronick, Victoria Fulidou, Lucinda A. Fulton, Robert S. Fulton, Stacey B. Gabriel, Jianjiong Gao, Qingsong Gao, Johanna Gardner, Julie M. Gastier-Foster, Carl M. Gay, Nils Gehlenborg, Mark Gerken, Gad Getz, Andrew K. Godwin, Eryn M. Godwin, Elena Gordienko, Juneko E. Grilley-Olson, David A. Gutman, David H. Gutmann, D. Neil Hayes, Apurva M. Hegde, David I. Heiman, Zachary Heins, Carmen Helsel, Austin J. Hepperla, Kelly Higgins, Katherine A. Hoadley, Shital Hobensack, Robert A. Holt, Dave B. Hoon, Jason L. Hornick, Alan P. Hoyle, Xin Hu, Mei Huang, Carolyn M. Hutter, Mary Iacocca, Davis R. Ingram, Michael Ittmann, Lisa Iype, Stuart R. Jefferys, Kevin B. Jones, Corbin D. Jones, Steven J.M. Jones, Tamara Kalir, Beth Y. Karlan, Apollon Karseladze, Katayoon Kasaian, Jaegil Kim, Ritika Kundra, Hanluen Kuo, Marc Ladanyi, Phillip H. Lai, Peter W. Laird, Erik Larsson, Michael S. Lawrence, Alexander J. Lazar, Sanghoon Lee, Darlene Lee, Kjong-Van Lehmann, Kristen M. Leraas, Jenny Lester, Douglas A. Levine, Irene Li, Tara M. Lichtenberg, Pei Lin, Jia Liu, Wenbin Liu, Eric Minwei Liu, Laxmi Lolla, Yiling Lu, Yussanne Ma, Rashna Madan, Dennis T. Maglinte, Anthony Magliocco, Robert G. Maki, David Mallery, Georgy Manikhas, Elaine R. Mardis, Armaz Mariamidze, Marco A. Marra, John A. Martignetti, Cathleen Martinez, Michael Mayo, Michael D. McLellan, Sam Meier, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, Christopher A. Miller, Gordon B. Mills, Richard A. Moore, Scott Morris, Lisle E. Mose, Evgeny Mozgovoy, Andrew J. Mungall, Karen Mungall, Michael Nalisnik, Rashi Naresh, Yulia Newton, Michael S. Noble, Janet E. Novak, Angelica Ochoa, Narciso Olvera, Taofeek K. Owonikoko, Oxana Paklina, Jeremy Parfitt, Joel S. Parker, Alessandro Pastore, Joseph Paulauskis, Robert Penny, Elena Pereira, Charles M. Perou, Amy H. Perou, Todd Pihl, Raphael E. Pollock, Olga Potapova, Amie J. Radenbaugh, Suresh S. Ramalingam, Nilsa C. Ramirez, W. Kimryn Rathmell, Chandrajit P. Raut, Richard F. Riedel, Colleen Reilly, Sheila M. Reynolds, Jeffrey Roach, A. Gordon Robertson, Jason Roszik, Brian P. Rubin, Sara Sadeghi, Gordon Saksena, Andrew Salner, Francisco Sanchez-Vega, Chris Sander, Jacqueline E. Schein, Heather K. Schmidt, Nikolaus Schultz, Steven E. Schumacher, Harman Sekhon, Yasin Senbabaoglu, Galiya Setdikova, Candace Shelton, Troy Shelton, Ronglai Shen, Yan Shi, Juliann Shih, Ilya Shmulevich, Gabriel L. Sica, Janae V. Simons, Samuel Singer, Payal Sipahimalani, Tara Skelly, Nicholas Socci, Heidi J. Sofia, Matthew G. Soloway, Paul Spellman, Qiang Sun, Patricia Swanson, Angela Tam, Donghui Tan, Roy Tarnuzzer, Nina Thiessen, Eric Thompson, Leigh B. Thorne, Pan Tong, Keila E. Torres, Matt van de Rijn, David J. Van Den Berg, Brian A. Van Tine, Umadevi Veluvolu, Roel Verhaak, Doug Voet, Olga Voronina, Yunhu Wan, Zhining Wang, Jing Wang, John N. Weinstein, Daniel J. Weisenberger, Matthew D. Wilkerson, Richard K. Wilson, Lisa Wise, Tina Wong, Winghing Wong, John Wrangle, Ye Wu, Matthew Wyczalkowski, Liming Yang, Christina Yau, Venkata Yellapantula, Jean C. Zenklusen, Jiashan (Julia) Zhang, Hailei Zhang, Hongxin Zhang, Erik Zmuda Keywords genomics; immune infiltration; The Cancer Genome Atlas; pleomorphism; DNA methylation; molecular subtype; dedifferentiated liposarcoma; leiomyosarcoma; undifferentiated pleomorphic sarcoma; myxofibrosarcoma Highlights * Multiplatform genetic analysis of 206 sarcomas of 6 types shows their diversity * Sarcomas harbor many more copy-number alterations than most other cancer types * Inferred immune microenvironment associates with outcome in multiple sarcoma types * Computed histologic nuclear pleomorphism correlates with aneuploidy estimates Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types. Author Affiliation: (1) Cancer Genome Atlas Program Office, National Cancer Institute at NIH, 31 Center Drive, Bldg. 31, Suite 3A20, Bethesda, MD 20892, USA * Corresponding author Article History: Received 17 March 2017; Revised 7 July 2017; Accepted 5 October 2017 (miscellaneous) Published: November 2, 2017 (footnote)2 Lead Contact (Alexander J. Lazar)